Scientist Look to "Scrub" Human Blood of Mad Cow Related Prions

An investigational approach to sifting infectious prions from donated
blood could help quell fears, focused in Britain, about the possible
spread by transfusion of variant Creutzfeldt-Jakob disease, researchers
here reported.

In a proof-of-concept study, no animals exposed to blood treated to
remove scrapie-causing prions developed the disease, whereas 15 of 99
animals exposed to untreated blood developed scrapie, reported Robert
G. Rohwer, Ph.D., of the University of Maryland, and colleagues, in the
Dec. 23 issue of The Lancet.

Scrapie is a transmissible spongiform encephalopathy similar to variant Creutzfeldt-Jakob disease (vCJD),

The
blood treatment method involves removing white cells from the blood
through leukoreduction, and then removing prions from the red-cell
concentrate using a technique commonly employed for purifying proteins
for drug research.

If
proven in further studies using animal and human blood, it could be an
a more effective alternative to the current practice in the U.S. and in
Britain of screening blood donors for possible s with people who
are known to have vCJD.

"Blood-associated
transmissible spongiform encephalopathy infectivity presents unique
challenges to risk management absent from other blood-borne pathogens,"
the investigators wrote. "The low concentration of infectivity,
although difficult to detect, has nevertheless been sufficient for
efficient transfusion transmission of these fatal diseases. People with
certain genotypes could harbor the infection in a transmissible but
undetectable form for decades."

In the Dec. 8 issue of The Lancet,
British researchers reported a third case of vCJD in an at-risk group
who were given tainted blood transfusions. The patient was the first to
be identified before death as having the disease. The 32-year-old man
developed the disease after a red-cell transfusion donated by a person
later determined to have vCJD.

Two
other cases -- identified after death and reported two years ago --
were previously identified among 66 people who got blood transfusions
from donors who subsequently developed vCJD, according to Stephen Wroe,
M.D., of the National Prion Clinic at the National Hospital for
Neurology and Neurosurgery in London.

The
American Red Cross asks all potential blood donors whether they have
ever had a blood relative with Creutzfeldt-Jakob disease, and whether
they had lived in the United Kingdom for at least three months since
1980, whether they had received a blood transfusion in England since
1980, or whether they had traveled or lived in Europe for a cumulative
five years or more since 1980.

The
questions are meant to tease out possible exposure to bovine spongiform
encephalopathy or vCJD, but the incubation period for human prion
diseases such as vCJD may be longer than 60 years, according to
researchers who studied the closely related disease kuru in former
cannibals in New Guinea.

That
research suggests that an epidemic of variant CJD could crop up decades
from now, with the aging of people who in the 1990s consumed beef from
cows infected with bovine spongiform encephalopathy, also known as
mad-cow disease, noted John Collinge, Ph.D., a professor of neurology
at University College London, and colleagues in Australia, and Papua
New Guinea, in the June 24 issue of The Lancet

In
fact, the incubation period for vCJD could be even longer than that of
kuru, because of a species-barrier effect that typically slows the rate
of interspecies transmission.

In
the current study, Dr. Rohwer and colleagues looked at the ability of
affinity resin chromatography to remove infectious prion particles from
the blood of hamsters infected with scrapie.

The technique involves the use of a specific ligand, selected from
among millions of possible candidates, that has high binding affinity
with both normal and abnormally folded proteins -- in this case, the
prion that causes scrapie.

The
authors looked at the ability of the affinity resin, labeled L13 and
mass-produced version of the same resin, labeled L13A, to remove
transmissible spongiform infectivity endogenously present in hamster
blood.

They
took 500 mL of scrapie-infected hamster whole blood and purged it of
white cells using leukoreduction. They then passed the red-cell
concentrate through columns of the affinity resins, with each sample
getting two pass-throughs. They then tested the samples for infectivity
by limiting dilution titration.

They
found that leukoreduction alone removed 72% of input infectivity, but
when they challenged a group of 99 hamsters with the leukoreduced but
unfiltered red cell concentrate, 15 of the animals became infected.

In
contrast, none of either 96 transfused with blood that had been passed
through the L13 affinity resin, nor any of the 100 animals exposed to
blood passed through the L13A resin, went on to develop the disease at
the last follow-up of 540 days.

The
limit of detection of the bioassay was 0.2 infectious doses per mL, and
the overall reduction of the challenge infectivity was more than 1.22
log10, the authors noted.

"The
results showed removal of endogenous transmissible spongiform
encephalopathy infectivity from leukoreduced whole blood by affinity
ligands," they wrote. "The same resins adsorb normal and abnormal prion
protein from human infections with variant, sporadic, and familial
Creutzfeldt-Jakob disease, in the presence of blood components."

But
assessing such technologies in the real world may be a good deal more
difficult, given that there is currently no assay sensitive enough to
reliably detect the disease in people with clinical vCJD, cautioned
Marc L. Turner, M.D., Ph.D., a clinical director of the Scottish
National Blood Transfusion Service and Chair of the vCJD Working Group
of the United Kingdom Transfusion Services Specialist Advisory
Committee on Transfusion Transmitted Infections.

"Until
these technologies can be clinically and operationally assessed, the
best protection against the uncertain risk of transfusion-associated
prion disease remains in ensuring that blood products are used only if
needed and that the uncertainties surrounding potential risks are
communicated effectively to patients and to the public at large," Dr.
Turner wrote in an accompanying editorial.

Dr. Rohwer and two of his co-authors are cofounders and
part owners of Pathogen Removal and Diagnostics Technologies, which
sponsored the study. Three of the other authors are employees of
ProMetic BioSciences, a joint venture partner in the development of the
removal resin, and two are employees of the American National Red
Cross, also a joint venture partner in the development of the resin.

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